University of Pittsburgh, Pittsburgh, PA; XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, PA; Pittsburgh VA Healthcare System, Pittsburgh, PA.
Am J Transplant. 2013 Oct;13(10):2619-33. doi: 10.1111/ajt.12424. Epub 2013 Sep 6.
We conducted a retrospective study of 17 transplant recipients with carbapenem-resistant Klebsiella pneumoniae bacteremia, and described epidemiology, clinical characteristics and strain genotypes. Eighty-eight percent (15/17) of patients were liver or intestinal transplant recipients. Outcomes were death due to septic shock (18%), cure (24%) and persistent (>7 days) or recurrent bacteremia (29% each). Thirty- and 90-day mortality was 18% and 47%, respectively. Patients who were cured received at least one active antimicrobial agent and underwent source control interventions. Forty-one percent (7/17) of patients had intra-abdominal infections; all except one developed persistent/recurrent bacteremia despite drainage. Two patients tolerated persistent bacteremia for >300 days. All patients except one were infected with sequence type 258 (ST258), K. pneumoniae carbapenemase (KPC)-2-producing strains harboring a mutant ompK35 porin gene; the exception was infected with an ST37, KPC-3-producing strain. Seventy-one percent (12/17) of patients were infected with ST258 ompK36 mutant strains. In two patients, persistent bacteremia was caused by two strains with different ompK36 genotypes. Three ompK36 mutations were associated with significantly higher carbapenem minimum inhibitory concentrations than wild-type ompK36. Pulse-field gel electrophoresis identified a single ST258 lineage; serial strains from individual patients were indistinguishable. In conclusion, KPC-K. pneumoniae bacteremia exhibited highly diverse clinical courses following transplantation, and was caused by clonal ST258 strains with different ompK36 genotypes.
我们对 17 例碳青霉烯类耐药肺炎克雷伯菌菌血症的移植受者进行了回顾性研究,描述了其流行病学、临床特征和菌株基因型。88%(15/17)的患者为肝或肠移植受者。结局为感染性休克导致的死亡(18%)、治愈(24%)以及持续性(>7 天)或复发性菌血症(各 29%)。30 天和 90 天死亡率分别为 18%和 47%。治愈的患者至少接受了一种有效的抗菌药物治疗,并进行了源头控制干预。41%(7/17)的患者存在腹腔内感染;除 1 例外,所有患者在引流后均发生持续性/复发性菌血症。2 例患者能够耐受持续性菌血症超过 300 天。除 1 例外,所有患者均感染了携带突变型 ompK35 孔蛋白基因的产 KPC-2 的肺炎克雷伯菌 ST258 型(258 型),1 例外感染了产 KPC-3 的 ST37 型。71%(12/17)的患者感染了 258 型 ompK36 突变株。在 2 例患者中,持续性菌血症是由两种具有不同 ompK36 基因型的菌株引起的。3 种 ompK36 突变与野生型 ompK36 相比,对碳青霉烯类的最小抑菌浓度显著升高。脉冲场凝胶电泳鉴定出单一的 258 型谱系;来自单个患者的连续菌株无法区分。总之,移植后 KPC-肺炎克雷伯菌菌血症表现出高度多样化的临床过程,由具有不同 ompK36 基因型的克隆 258 型菌株引起。